Fremont-Smith started working in the 1920s at the department of neuropathology at the Harvard Medical School in Boston, Massachusetts. He was married to Frances Hopkinson Fremont-Smith, and the youngest of their three sons was Eliot Fremont-Smith (1929-2007) a former critic for the New York Times.[2]

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Fremont-Smith was familiar with what would become cybernetics' prehistory, because of his involvement in the 1930s in an informal conversational network around neurophysiology and the work of Walter Cannon on homeostasis.[1]

A second initiative he organized in the 1940s was a meeting about "physiological mechanisms underlying the phenomena of conditioned reflexes and hypnosis as related to the problem of cerebral inhibition."[3] This socalled "Cerebral Inhibition Meeting" was sponsored by the Josiah Macy Foundation attended by scientists like Gregory Bateson, and Margaret Mead, and five others. Together they would initiated the Cybernetics Group. Among its members this group was as called the "Man-Machine Project". Other participants were Warren McCulloch, Arturo Rosenblueth, Gregory Bateson, Margaret Mead, and Lawrence K. Frank. According to Steinberg (2000) "Rosenblueth, a protégé of Norbert Wiener, set out the broad parameters of the proposed effort.

Between 1946 and 1953 Fremont-Smith worked as Medical Director in the Macy Foundation, when ten Macy Conferences were a set of meetings of scholars from various disciplines held to discuss "Circular Causal and Feedback Mechanisms in Biological and Social Systems".[4] It was one of the first organized studies of interdisciplinarity, spawning breakthroughs in systems theory and leading to the foundation of what later was to be known as cybernetics. End 1950s he was among the first members of the Society for General Systems Research.

In 1959 Frank Fremont-Smith, as head of the Macy foundation, was the organizer of the first ever held conferences on LSD.[3] When Fremont-Smith retired as the Foundation's Medical Director, he was encouraged to apply the concept of Interdisciplinary Communications Program (ICP) to the field of the biological sciences in general. He began the series Interdisciplinary Communications Program (1968-1976) at the Smithsonian Institution.[5]